Although probabilistic analysis has become the accepted standard for decision analytic cost-effectiveness models, deterministic one-way sensitivity analysis continues to be used to meet the need of decision makers to understand the impact that changing the value taken by one specific parameter has on the results of the analysis. The value of a probabilistic form of one-way sensitivity analysis has been recognised, but the proposed methods are computationally intensive. Deterministic one-way sensitivity analysis provides decision makers with biased and incomplete information whereas, in contrast, probabilistic one-way sensitivity analysis (POSA) can overcome these limitations, an observation supported in this study by results obtained when these methods were applied to a previously published cost-effectiveness analysis to produce a conditional incremental expected net benefit curve. The application of POSA will provide decision makers with unbiased information on how the expected net benefit is affected by a parameter taking on a specific value and the probability that the specific value will be observed.

These data suggest that incidence and prevalence of HIV may have increased, whereas other indicators suggest an increase in risk behaviour. It is critical that harm reduction measures are reinvigorated, and evolve in response to changes in drug use risk behaviours and policy.

Background:The purpose of this study was to determine the accuracy of sentinel lymph node (SLN) biopsy with technetium 99 (99mTc) and/or blue dye-enhanced lymphoscintigraphy in vulval cancer.Methods:Sensitive searches of databases were performed upto October 2013. Studies with at least 75% of women with FIGO stage IB or II vulval cancer evaluating SLN biopsy with 99mTc, blue dye or both with reference standard of inguinofemoral lymphadenectomy (IFL) or clinical follow-up were included. Meta-analyses were performed using Meta-Disc version 1.4.Results:Of the 2950 references, 29 studies (1779 women) were included; most of them evaluated 99mTc combined with blue dye. Of these, 24 studies reported results for SLN followed by IFL, and 5 reported clinical follow-up only for SLN negatives. Pooling of all studies was inappropriate because of heterogeneity. Mean SLN detection rates were 94.0% for 99mTc, 68.7% for blue dye and 97.7% for both. SLN biopsy had pooled sensitivity of 95% (95% CI 92–98%) with negative predictive value (NPV) of 97.9% in studies using 99mTc/blue dye, ultrastaging and immunohistochemistry with IFL as reference. Pooled sensitivity for SLN with clinical follow-up for SLN-negatives was 91% (85–95%) with NPV 95.6%. Patients undergoing SLN biopsy experienced less morbidity than those undergoing IFL.Conclusions:Sentinel lymph node biopsy using 99mTC, blue dye and ultrastaging with immunohistochemistry is highly accurate when restricted to carefully selected patients, within a rigorous protocol, with close follow-up and where sufficient numbers for learning curve optimisation exist. Patients must make an informed choice between the slightly higher groin recurrence rates of SLN biopsy vs the greater morbidity of IFL.

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BackgroundUncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations.Methods/designIohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components:1) A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of South-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR ≥30 mg/mmol) will comprise 20-30% of the study cohort.2) A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.3) A biological variability study to establish reference change values for reference and test measures.4) A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).5) A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline.DiscussionThe eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice.Trial registrationISRCTN42955626.